The levels of circulating cytokines and risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study

Front Immunol. 2024 Jul 1:15:1418309. doi: 10.3389/fimmu.2024.1418309. eCollection 2024.

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease affecting the central nervous system (CNS). NMOSD pathogenesis involves systemic inflammation. However, a causal relationship between circulating cytokine levels and NMOSD remains unclear.

Methods: Mendelian randomization (MR) approaches were used to investigate the potential association between genetically determined circulating 19 inflammatory cytokines and 12 chemokines levels and the risk of developing NMOSD.

Results: After Bonferroni correction, the risk of aquaporin 4-antibody (AQP4-ab)-positive NMOSD was suggested to be causally associated with the circulating levels of three cytokines, including interleukin (IL)-4 [odds ratio (OR): 11.01, 95% confidence interval (CI): 1.16-104.56, P = 0.037], IL-24 (OR: 161.37; 95% CI: 2.46-10569.21, P = 0.017), and C-C motif chemokine 19 (CCL19) (OR: 6.87, 95% CI: 1.78-26.93, P = 0.006).

Conclusion: These findings suggest that a genetic predisposition to higher levels of IL-4, IL-24, and CCL19 may exert a causal effect on the risk of AQP4-ab-positive NMOSD. Further studies are warranted to clarify how these cytokines affect the development of AQP4-ab-positive NMOSD.

Keywords: Mendelian randomization; chemokine; cytokine; inflammation; neuromyelitis optica spectrum disorder.

MeSH terms

  • Aquaporin 4 / genetics
  • Aquaporin 4 / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Cytokines* / blood
  • Genetic Predisposition to Disease*
  • Humans
  • Mendelian Randomization Analysis*
  • Neuromyelitis Optica* / blood
  • Neuromyelitis Optica* / genetics
  • Neuromyelitis Optica* / immunology
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • Cytokines
  • Aquaporin 4
  • Autoantibodies

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (Nos: 82301531 and 82171339), the Key Research and Development Project of Shaanxi Province (No: 2022ZDLSF02-04), and the Youth Innovation Team of Shaanxi Universities (2023-997-71).